title: Short telomere lengths in peripheral blood leukocytes are associated with an increased risk of oral premalignant lesion and oral squamous cell carcinoma.
abstract: BACKGROUND
  Oral premalignant lesions (OPLs) are precursors of oral squamous cell carcinoma (OSCC). Short telomeres in peripheral blood leukocytes (PBLs) are associated with increased risks of several cancers. However, it is unclear whether short leukocyte telomere length (LTL) predisposes individuals to OPL and OSCC.
  
  
  METHODS
  LTL was measured in PBLs from 266 patients who had a diagnosis of either OPL (N = 174) or OSCC (N = 92) and from 394 age-matched and sex-matched controls. The association between LTL and the risk of OPL or OSCC, as well as the interaction of telomere length, cigarette smoking, and alcohol drinking on the risk of OPL or OSCC, were analyzed.
  
  
  RESULTS
  The age-adjusted relative LTL was shortest in the OSCC group (1.64 ± 0.29), intermediate in the OPL group (1.75 ± 0.43), and longest in the control group (1.82 ± 0.36; Ptrend < .001). When the analysis was dichotomized at the median value in controls, adjusting for age, sex, smoking status, and alcohol drinking status, the odds ratio for the risk of OPL and OSCC associated with short LTL was 2.03 (95% confidence interval, 1.29-3.21) and 3.47 (95% CI, 1.84-6.53), respectively, with significant dose-response effects for both associations. Among 174 patients with OPL, 23 progressed to OSCC, and the mean LTL was shorter in progressors than in nonprogressors (mean ± standard deviation: 1.66 ± 0.35 vs 1.77 ± 0.44, respectively), although the difference did not reach statistical significance (P = .258), probably because of the small number of progressors. An interaction analysis identified short LTL, smoking, and drinking alcohol as independent risk factors for OPL and OSCC.
  
  
  CONCLUSIONS
  Short LTL was associated with increased risks of developing OPL and OSCC. The current results also indicated that short LTL likely predisposes patients to the malignant progression of OPL.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Center, Houston, Texas; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Enping
authors.initials: E
authors.lastname: Xu
authors.forename: Yilei
authors.initials: Y
authors.lastname: Gong
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000235:genetics / Q000473:pathology; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059506:Telomere Shortening
keywords: alcohol drinking; oral premalignant lesion; oral squamous cell carcinoma; peripheral blood leukocytes; smoking; telomere length